CLSTN2 p.Ile124=
c.372C>A · rs74507604 · VCV786022
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.66%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP 0.96, phastCons 1 |
| Overall | ||
| CADD | 13.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.66%
African / African-American · 3,498/75,024 alleles
Filtering AF
4.53%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.48%
Overall
0.253%
4,082/1,614,126 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.66% | 21 |
| Admixed American | 0.407% | 246 |
| Remaining individualsnot grpmax-eligible | 0.389% | 257 |
| Middle Eastern | 0.347% | 289 |
| South Asian | 0.0143% | 7,006 |
| European (non-Finnish) | 0.00534% | 18,730 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CLSTN2
- Protein
- p.Ile124=
- Coding
- c.372C>A
- MANE Select
- NM_022131
- dbSNP
- rs74507604
- Type
- single nucleotide variant
- Location
- chr3:140403768 (GRCh38)
- Gene constraint
- LOEUF 0.578 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.46
- Residue 124
- the cadherin 1 domain
Similar variants
- CLSTN2 c.233-8T>G Benign ★★ same type
- CLSTN2 p.Gly776= Benign ★★ same type
- CLSTN2 p.Ile306Asn Likely benign ★★ ⚠ same type
- CLSTN2 p.Ala131Thr Uncertain significance ★ ⚠ same type
- CLSTN2 p.Ala137Asp Uncertain significance ★ ⚠ same type
- CLSTN2 p.Ala243Thr Uncertain significance ★ ⚠ same type
- CLSTN2 p.Ala326Asp Uncertain significance ★ ⚠ same type
- CLSTN2 p.Ala440Val Uncertain significance ★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/clstn2-p-ile124 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown